This program project is focused on the major medical complications of genital HSV infection. The first Project evaluates the interaction between HSV and HIV-1. Studies to evaluate if abrogation of HSV shedding by acyclovir reduces HIV 1 replication on mucosal surfaces and lymphoid tissue are described. HIV-1 quasispecies evolution and measurement of reservoirs of HIV-1 in cells and lymphoid tissue will be performed. Studies to determine if HSV-2 infection increases HIV-1 transmission among HIV-1 discordant couples and whether acyclovir reduces HIV-1 acquisition among HSV-2 seropositive persons are also proposed. The second Project, Maternal Morbidity and Complications of Genital Herpes is directed at determining if serological screening and counseling will reduce high-risk sexual behavior among pregnant women at risk of acquiring genital herpes. Clinical trials are proposed to develop a short course chemoprophylaxis regimen with oral and IV acyclovir analogous to Group B strep prevention. Specific Aim 3 describes the development of a rapid assay to detect HSV DNA by PCR at labor and delivery. A cost utility analysis on strategies to improve the management of the HSV-2 seropositive pregnant women is also proposed. The third Project Lymphocyte Trafficking of Genital HSV-2 Infections. HSV specific CD8 T -cells of chronically infected persons with HSV-2 express the homing molecule CLA and this molecule is acquired during the course of infection. Studies to determine the role of CLA and other surface homing molecules on HSV specific T cells or effectors function are described. The four cores associated with the PO-1 are a Clinical Core directed at enrolling patients into the proposed trials, a Laboratory Core which performs all the HSV and HIV serological assays, HSV PCR and HIV molecular assays utilized in these studies. A Statistical Core is devoted to study-design, data management and analyses and a small Administrative Core. Collaborations with investigators in Peru, Zambia, Zimbabwe, Cameroon and Canada are proposed.